High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution

Tongo, Marcel; Dorfman, Jeffrey Robert; Martin, Darren Patrick

High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution

dc.contributor.author	Tongo, Marcel
dc.contributor.author	Dorfman, Jeffrey Robert
dc.contributor.author	Martin, Darren Patrick
dc.coverage.spatial	Congo basin	en_ZA
dc.date.accessioned	2017-09-14T13:41:18Z
dc.date.available	2017-09-14T13:41:18Z
dc.date.issued	2016-03-15
dc.description.abstract	The existence of various highly divergent HIV-1 lineages and of recombination-derived sequence tracts of indeterminate origin within established circulating recombinant forms (CRFs) strongly suggests that HIV-1 group M (HIV-1M) diversity is not fully represented under the current classification system. Here we used a fully exploratory screen for recombination on a set of 480 near-full-length genomes representing the full known diversity of HIV-1M. We decomposed recombinant sequences into their constituent parts and then used maximum-likelihood phylogenetic analyses of this mostly recombination-free data set to identify rare divergent sequence lineages that fall outside the major named HIV-1M taxonomic groupings. We found that many of the sequence fragments occurring within CRFs (including CRF04_cpx, CRF06_cpx, CRF11_cpx, CRF18_cpx, CRF25_cpx, CRF27_cpx, and CRF49_cpx) are in fact likely derived from divergent unclassified parental lineages that may predate the current subtypes, even though they are presently identified as derived from currently defined HIV-1M subtypes. Our evidence suggests that some of these CRFs are descended predominantly from what were or are major previously unidentified HIV-1M lineages that were likely epidemiologically relevant during the early stages of the HIV-1M epidemic. The restriction of these divergent lineages to the Congo basin suggests that they were less infectious and/or simply not present at the time and place of the initial migratory wave that triggered the global epidemic. IMPORTANCE HIV-1 group M (HIV-1M) likely spread to the rest of the world from the Congo basin in the mid-1900s (N. R. Faria et al., Science 346:56-61, 2014, http://dx.doi.org/10.1126/science.1256739) and is today the principal cause of the AIDS pandemic. Here, we show that large sequence fragments from several HIV-1M circulating recombinant forms (CRFs) are derived from divergent parental lineages that cannot reasonably be classified within the nine established HIV-1M subtypes. These lineages are likely to have been epidemiologically relevant in the Congo basin at the onset of the epidemic. Nonetheless, they appear not to have undergone the same explosive global spread as other HIV-1M subtypes, perhaps because they were less transmissible. Concerted efforts to characterize more of these divergent lineages could allow the accurate inference and chemical synthesis of epidemiologically key ancestral HIV-1M variants so as to directly test competing hypotheses relating to the viral genetic factors that enabled the present pandemic.	en_ZA
dc.identifier.apacitation	Tongo, M., Dorfman, J. R., & Martin, D. P. (2016). High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution. <i>Journal of Virology</i>, http://hdl.handle.net/11427/25212	en_ZA
dc.identifier.chicagocitation	Tongo, Marcel, Jeffrey Robert Dorfman, and Darren Patrick Martin "High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution." <i>Journal of Virology</i> (2016) http://hdl.handle.net/11427/25212	en_ZA
dc.identifier.citation	Tongo M, et al. J Virology 90(5):2221-2229 (2015) doi: 10.1128/JVI.02302-15.	en_ZA
dc.identifier.ris	TY - Journal Article AU - Tongo, Marcel AU - Dorfman, Jeffrey Robert AU - Martin, Darren Patrick AB - The existence of various highly divergent HIV-1 lineages and of recombination-derived sequence tracts of indeterminate origin within established circulating recombinant forms (CRFs) strongly suggests that HIV-1 group M (HIV-1M) diversity is not fully represented under the current classification system. Here we used a fully exploratory screen for recombination on a set of 480 near-full-length genomes representing the full known diversity of HIV-1M. We decomposed recombinant sequences into their constituent parts and then used maximum-likelihood phylogenetic analyses of this mostly recombination-free data set to identify rare divergent sequence lineages that fall outside the major named HIV-1M taxonomic groupings. We found that many of the sequence fragments occurring within CRFs (including CRF04_cpx, CRF06_cpx, CRF11_cpx, CRF18_cpx, CRF25_cpx, CRF27_cpx, and CRF49_cpx) are in fact likely derived from divergent unclassified parental lineages that may predate the current subtypes, even though they are presently identified as derived from currently defined HIV-1M subtypes. Our evidence suggests that some of these CRFs are descended predominantly from what were or are major previously unidentified HIV-1M lineages that were likely epidemiologically relevant during the early stages of the HIV-1M epidemic. The restriction of these divergent lineages to the Congo basin suggests that they were less infectious and/or simply not present at the time and place of the initial migratory wave that triggered the global epidemic. IMPORTANCE HIV-1 group M (HIV-1M) likely spread to the rest of the world from the Congo basin in the mid-1900s (N. R. Faria et al., Science 346:56-61, 2014, http://dx.doi.org/10.1126/science.1256739) and is today the principal cause of the AIDS pandemic. Here, we show that large sequence fragments from several HIV-1M circulating recombinant forms (CRFs) are derived from divergent parental lineages that cannot reasonably be classified within the nine established HIV-1M subtypes. These lineages are likely to have been epidemiologically relevant in the Congo basin at the onset of the epidemic. Nonetheless, they appear not to have undergone the same explosive global spread as other HIV-1M subtypes, perhaps because they were less transmissible. Concerted efforts to characterize more of these divergent lineages could allow the accurate inference and chemical synthesis of epidemiologically key ancestral HIV-1M variants so as to directly test competing hypotheses relating to the viral genetic factors that enabled the present pandemic. DA - 2016-03-15 DB - OpenUCT DP - University of Cape Town J1 - Journal of Virology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution TI - High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution UR - http://hdl.handle.net/11427/25212 ER -	en_ZA
dc.identifier.uri	http://hdl.handle.net/11427/25212
dc.identifier.vancouvercitation	Tongo M, Dorfman JR, Martin DP. High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution. Journal of Virology. 2016; http://hdl.handle.net/11427/25212.	en_ZA
dc.language	eng	en_ZA
dc.publisher	American Society of Microbiology	en_ZA
dc.publisher.department	Division of Immunology	en_ZA
dc.publisher.faculty	Faculty of Health Sciences	en_ZA
dc.publisher.institution	University of Cape Town
dc.source	Journal of Virology	en_ZA
dc.source.uri	http://jvi.asm.org/site/misc/about.xhtml
dc.title	High Degree of HIV-1 group M Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution	en_ZA
dc.type	Journal Article	en_ZA
uct.type.filetype	Text
uct.type.filetype	Image
uct.type.publication	Research	en_ZA
uct.type.resource	Article	en_ZA